title: Simultaneous intake of oat bran and atorvastatin reduces their efficacy to lower lipid levels and atherosclerosis in LDLr-/- mice.
abstract: The present study aimed to investigate the effects of separate and simultaneous dietary intake of atorvastatin (ATO) and the soluble fiber oat bran on serum and hepatic lipid levels and the degree of atherosclerosis. Ninety female LDL-receptor-deficient (LDLr-/-) mice were fed a Western-type diet containing either low dose (0.0025%), high dose (0.01%) or no ATO, with or without oat bran (27%) (n=15 per group) for 16 weeks. Both ATO and oat bran were effective in reducing serum total cholesterol levels (low ATO: -5.48, high ATO: -9.12, oat bran: -3.82 mmol/l, compared to control (no ATO/no oat bran), all p<0.0001). When oat bran was added to a low dose ATO, the cholesterol-lowering effects of this combination were 50% smaller compared to the low dose ATO diet alone (between-group difference: 2.77 mmol/l, p=0.002), whereas total cholesterol decreased to a similar extent in the groups fed a high dose ATO, with or without oat bran (between-group difference: 1.10 mmol/l, p=0.21). Serum LDL- and HDL-cholesterol, triglycerides, hepatic lipid levels and atherosclerotic lesion development showed a similar pattern. In conclusion, the efficacy of oat bran and atorvastatin to lower lipid levels and atherosclerosis is reduced after simultaneous intake. We hypothesize that oat bran inhibits the intestinal absorption of atorvastatin, and consequently its cholesterol-lowering effects. The effects are likely dependent on the type of statin and dietary fiber, and on the relative timing of intake of the statin and the dietary fiber. Future studies should focus on these aspects to provide further insight into the exact mechanism of this food-drug interaction.
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands. S.Eussen@uu.nl
authors.forename: Simone R B M
authors.initials: SR
authors.lastname: Eussen
authors.forename: Cathy J M
authors.initials: CJ
authors.lastname: Rompelberg
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Andersson
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
authors.forename: Per
authors.initials: P
authors.lastname: Hellstrand
authors.forename: Rickard
authors.initials: R
authors.lastname: Oste
authors.forename: Henk
authors.initials: H
authors.lastname: van Kranen
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000178:diet therapy* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069059:Atorvastatin; D018554:Avena / Q000737:chemistry*; D001769:Blood / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003131:Combined Modality Therapy / Q000379:methods; D004043:Dietary Fiber / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D004435:Eating / Q000187:drug effects; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D007408:Intestinal Absorption / Q000187:drug effects; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000178:diet therapy / Q000188:drug therapy / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D011973:Receptors, LDL / Q000235:genetics*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D047071:beta-Glucans / Q000032:analysis
chemical_list: D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004043:Dietary Fiber; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D011973:Receptors, LDL; D014280:Triglycerides; D047071:beta-Glucans; D002784:Cholesterol; D000069059:Atorvastatin